Chronic and Acute Drug-Induced Hypersensitivity Syndrome in a Rural Patient With Cytomegalovirus Infection: A Case Report.

A 50-year-old man presented with fever and a generalized rash, with chronic fatigue and lymphadenopathy for a year and a half. Initial tests ruled out lymphoproliferative disorders, showing reactive hyperplasia and cytomegalovirus. Symptoms worsened after ampicillin treatment, leading to suspected drug-induced hypersensitivity syndrome (DIHS). Upon admission, amoxicillin was discontinued, and prednisolone and antiviral treatment were initiated. The patient's condition improved with this therapy. A drug-induced lymphocyte stimulation test confirmed hypersensitivity to both ampicillin and allopurinol. This case illustrates the diagnostic challenge of chronic and acute DIHS because of the rare presentation. It underscores the need for high suspicion of DIHS in patients with chronic lymphadenopathy and fatigue, particularly with recent drug exposure. Effective management involves recognizing symptoms, withdrawing the offending drug, and using corticosteroids. Viral infections like cytomegalovirus can complicate DIHS diagnosis and treatment, necessitating a comprehensive approach. This case highlights the importance of considering DIHS in differential diagnoses and the complexities of managing it alongside co-infections in rural healthcare settings.

Unmanageable Cerebrospinal Fluid Leakage With Eosinophilic Meningitis in a Gliadel Wafer Implant Patient.

Gliadel wafer implants (Eisai Inc., Woodcliff Lake, NJ, USA) have shown their efficacy in prolonging survival in patients with malignant gliomas. The safety of Gliadel wafers has also been reported; however, there is a certain risk of adverse events. We present a rare case of refractory cerebrospinal fluid (CSF) leakage with eosinophilic meningitis in a patient with glioblastoma who underwent tumor resection with Gliadel wafer implants. A 60-year-old man presented with a glioblastoma in the right temporal lobe. The patient underwent tumor resection with Gliadel wafer implants. During the postoperative course, the patient presented with intractable CSF leakage and the development of a pseudomeningocele. A delayed rise in blood and CSF eosinophil count (a few weeks after the primary operation) and positive drug-induced lymphocyte stimulation test (DLST) results against the Gliadel wafer led to the diagnosis of an allergic reaction to these implants. Removal of the Gliadel wafers resolved the eosinophilic reaction; however, the patient subsequently required a shunt procedure for persistent hydrocephalus. This case highlights the importance of investigating rare causes of refractory CSF leakage and hydrocephalus due to allergic reactions to Gliadel wafers. Delayed elevations of eosinophils in blood and CSF tests may lead to a diagnosis of eosinophilic meningitis. DLST against Gliadel wafers is also useful for diagnosis when it is available. To control the hydrocephalus, not only the shunt procedure but also wafer removal must be considered; however, patients with limited life expectancy are generally hesitant to undergo such additional procedures.

Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome to Hemodialysis Polysulfone Membrane.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe and potentially life-threatening hypersensitivity reaction. Although commonly associated with specific drugs, there have been no reports of DRESS syndrome caused by medical devices. We report a unique case of DRESS syndrome linked to a particular hemodialysis membrane during treatment. An 83-year-old man on hemodialysis exhibited fever, rash, and elevated eosinophils. Despite medication changes and consultations with specialists, his condition persisted. A drug-induced lymphocyte stimulation test revealed a positive response to the dialysis membrane. His symptoms and lab results met DRESS syndrome diagnostic criteria. After substituting the membrane and administering glucocorticoids, the patient displayed early improvement. Diagnosing DRESS syndrome is complex due to its varied presentation and lack of specific benchmarks. This instance underscores the need to consider medical devices as potential DRESS syndrome triggers. Enhanced physician awareness can facilitate prompt detection and proper management, ultimately refining patient outcomes.

The Possibility of Acute Drug-Induced Liver Injury Associated With Prednisolone.

A female patient was referred to our hospital with complaints of liver injury. She had been treated for immunoglobulin (Ig)A nephropathy using prednisolone and other medications. Drug-induced liver injury (DILI) was suspected, as no evidence of viral infection or autoimmune liver disease was apparent. All medications except for prednisolone were discontinued, but liver enzyme levels remained elevated. Percutaneous liver biopsy showed the characteristics of DILI and drug lymphocyte stimulation testing yielded positive results for prednisolone. After stopping administration of prednisolone, liver enzyme levels recovered to near-normal. Prednisolone has immunosuppressive effects and is sometimes used to treat DILI. Some reports have revealed that high-dose corticosteroids can induce liver injury, but liver injuries associated with low-dose corticosteroid therapy have not been described. Prednisolone-induced liver injury is a rare phenomenon. When low-dose corticosteroids are used for treatment, care should be taken regarding the possibility of liver injury.

Acute Tubulointerstitial Nephritis due to Human Papillomavirus Vaccination.

Acute tubulointerstitial nephritis (ATIN), a rare cause of acute kidney injury in children, is caused by various factors such as drugs, infection, and systemic inflammation. We herein present a case of ATIN with mild encephalitis/encephalopathy with reversible splenial lesion (MERS)-like findings on head magnetic resonance imaging (MRI), which was associated with human papillomavirus (HPV) vaccination. A 14-year-old girl presented to our hospital with a high fever for 5 days. Results of common laboratory tests were normal except for increased C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR). Antibiotics were administered, and the fever promptly resolved after admission. After 7 weeks, she was readmitted due to a high fever for 4 days. In addition to increased CRP levels and ESR, urine test revealed high urine N-acetyl-ß-D-glucosaminidase and ß-2-microglobulin levels, and a renal scintigram showed mild bilateral uptake of 67Ga-citrate, consistent with the pathology of ATIN. Furthermore, head MRI, which was performed because the patient experienced prolonged headaches, revealed MERS-like lesions, although she did not have other neurological symptoms. Detailed examination of her medical records revealed that she had developed high fever 10 days after the third HPV vaccination and another previous episode of high fever 12 weeks after the second HPV vaccination. Based on these findings, we concluded that the ATIN and MERS-like lesions could have been associated with HPV vaccination. Although HPV vaccination is important for preventing uterine cancer, physicians must be vigilant about its various potential adverse effects, including ATIN.

Acetaminophen-induced liver injury at therapeutic doses in a young adult: a case report.

Acetaminophen causes volume-dependent hepatotoxicity; however, hepatotoxicity may also occur with acetaminophen administered at normal doses. We encountered a case of allergic liver damage in a 17-year-old girl receiving acetaminophen at a regular dose. The patient was diagnosed using the Roussel Uclaf Causality Assessment Method (RUCAM) and the diagnostic scale of the Digestive Disease Week Japan 2004 workshop. She tested positive for acetaminophen on a drug-induced lymphocyte stimulation test, and liver biopsy results confirmed the diagnosis of acetaminophen-induced liver injury. Despite administering acetaminophen at normal doses, hepatotoxicity may occur, which warrants further exploration.

Clarithromycin-induced eosinophilic granulomatosis with polyangiitis: A case report.

A 75-year-old man presented to our hospital with chronic sinusitis, bronchiectasis, and chronic lower respiratory tract infections. He began taking erythromycin in August, X-2. The chronic lower respiratory tract infection gradually worsened, and clarithromycin was started on May 11, X. He became aware of fever and numbness in his lower legs on June 4, X. The sign occurred soon after oral clarithromycin and blood tests showed an elevated eosinophil count and C-reactive protein (CRP) levels, positive MPO-ANCA antibodies, and positive for drug-induced lymphocyte stimulation test (DLST); we diagnosed eosinophilic granulomatosis with polyangiitis (EGPA) associated with clarithromycin administration.

Food protein-induced enterocolitis syndrome due to buckwheat: A case report.

Buckwheat is a rare causative food for food protein-induced enterocolitis syndrome (FPIES). To date, it is unknown what laboratory data patients with FPIES caused by buckwheat show. We report a 4-year-old female with FPIES caused by buckwheat and the laboratory results. Skin prick, specific IgE antibody, and basophil activation tests were negative; however, the lymphocyte stimulation test (LST) revealed a 10.2-fold increase in activation compared with the negative control. In an open-label oral food challenge (OFC) of 80 g boiled buckwheat noodles, 3 hours after ingestion, vomiting occurred four times in a 2-hour duration. Therefore, we diagnosed the patient with FPIES caused by buckwheat. Her neutrophil count, C-reactive protein, and thymus and activation-regulated chemokine were elevated after the OFC. Moreover, the patient had a positive reaction to the LST, which may theoretically be useful in diagnosing non-immunoglobulin E-mediated gastrointestinal food allergies. FPIES caused by buckwheat is rare; however, we found that the same laboratory results were observed in a comparison of FPIES cases caused by other foods.

Food protein-induced enterocolitis syndrome due to buckwheat: A case report

Buckwheat is a rare causative food for food protein–induced enterocolitis syndrome (FPIES). To date, it is unknown what laboratory data patients with FPIES caused by buckwheat show. We report a 4-year-old female with FPIES caused by buckwheat and the laboratory results. Skin prick, specific IgE antibody, and basophil activation tests were negative; however, the lymphocyte stimulation test (LST) revealed a 10.2-fold increase in activation compared with the negative control. In an open-label oral food challenge (OFC) of 80 g boiled buckwheat noodles, 3 hours after ingestion, vomiting occurred four times in a 2-hour duration. Therefore, we diagnosed the patient with FPIES caused by buckwheat. Her neutrophil count, C-reactive protein, and thymus and activation-regulated chemokine were elevated after the OFC. Moreover, the patient had a positive reaction to the LST, which may theoretically be useful in diagnosing non-immunoglobulin E-mediated gastrointestinal food allergies. FPIES caused by buckwheat is rare; however, we found that the same laboratory results were observed in a comparison of FPIES cases caused by other foods (AU)

A case of bunashimeji mushroom-induced hypersensitivity pneumonitis diagnosed by inhalational provocation test in a hospital room.

A 66-year-old woman was admitted to our hospital with a 2-month history of dry cough and exertional dyspnea. She had worked as a mushroom farmer and had been exposed to mushroom for more than 40 years. The patient showed elevated levels of KL-6 (2966 U/mL) and surfactant protein D (410 ng/mL), and computed tomography of the chest revealed ground-glass opacities and fine nodular shadows in both lungs, suggesting mushroom-induced hypersensitivity pneumonitis. Pulmonary function testing revealed decreases in forced vital capacity (78% of predicted) and carbon monoxide diffusing capacity (67% of predicted). The inhalational provocation test was positive for bunashimeji mushrooms. Precipitating antibody was only identified for spores or bodies of bunashimeji mushrooms, and lymphocyte stimulation testing with spores or bodies of bunashimeji mushrooms also yielded positive results. Bunashimeji mushroom-induced hypersensitivity pneumonitis was therefore diagnosed. Radiological findings and pulmonary function were improved by corticosteroid therapy and the patient has since remained healthy with allergen avoidance.

Acetaminophen-induced Stevens-Johnson syndrome with lethal lung injury: A case report.

Stevens-Johnson syndrome (SJS) with respiratory distress can lead to fatal outcomes. However, there are a few reports of drug-induced lung injury with diffuse alveolar damage caused by acetaminophen, the most severe type. Here, we describe a fatal case of acetaminophen-induced SJS in a child with irreversible lung lesions.

Clozapine-specific proliferative response of peripheral blood-derived mononuclear cells in Japanese patients with clozapine-induced agranulocytosis.

BACKGROUND: Although clozapine-induced granulocytopenia (CIG) is less severe than clozapine-induced agranulocytosis (CIA), and some patients with CIG may not go on to develop serious complications, clozapine is discontinued in cases of both CIA and CIG. Understanding the pathogenic mechanisms of CIA/CIG could provide better management of clozapine therapy. Recently, as a mechanistic insight into adaptive immune systems, European groups reported clozapine-specific proliferative responses and clozapine-specific T cells using blood taken from patients with CIA and/or CIG. AIMS: The aims of our study are to support this mechanistic evidence and to investigate the difference in the lymphocyte response to clozapine between patients with CIG and those with CIA. METHODS: Lymphocyte stimulation tests (LSTs) were conducted using CD25-positive cell-depleted peripheral blood-derived mononuclear cells (PBMCs) isolated from blood of four Japanese patients with CIA, four patients with CIG, and nine clozapine-tolerant subjects. RESULTS: Three of four patients with CIA and one of four patients with CIG showed proliferative responses to clozapine with a stimulation index of greater than 2. In contrast, none of the nine clozapine-tolerant subjects showed any response to clozapine. Olanzapine did not stimulate PBMCs of patients with CIA, patients with CIG, or clozapine-tolerant subjects. CONCLUSIONS: Clozapine- and CIA-specific lymphocyte reactions in a Japanese population provided supportive evidence that the pathogenesis of CIA is based on adaptive immune reactions. In addition, patients with CIG who show a positive response to an LST may at the very least not be chosen for clozapine-rechallenge and further prospective studies are desirable to verify this hypothesis.

Food Protein-induced Enterocolitis Syndrome Due to Rice in a Japanese Infant: A Case Report.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food allergy characterized by repetitive vomiting within 1-4 h and/or diarrhea within 24 h after ingesting the causative food. We herein report a rare Japanese case of rice-induced FPIES. A six-month-old, female, Japanese patient presented to the emergency room (ER) with the complaint of vomiting after feeding. Postprandial vomiting had occurred occasionally since she started ingesting solid food at the age of 5 months. Rice-induced FPIES was suspected only after the fourth ER visit based on the characteristic history of recurrent vomiting occurring 1-2 h after ingesting food containing rice. Allergen-specific IgE testing and a skin prick test with an allergen scratch extract were both negative for rice. During an oral food challenge test (OFC), vomiting was observed after the patient ingested 2 g of rice porridge. Based on the OFC results and the entire clinical course, FPIES due to rice was diagnosed. A lymphocyte stimulation test with rice revealed a significantly elevated stimulation index. Rice-induced FPIES is rarely reported among Japanese infants despite rice being a staple in the Japanese diet. The prevalence of rice-induced FPIES differs greatly among populations, suggesting a multifactorial cause associated with its development. Delays in diagnosis are common in FPIES, and our case demonstrates the importance of obtaining a dietary history of food ingested prior to symptom onset in cases of infantile repetitive vomiting.

Unilateral methotrexate-induced lung injury with foreign bodies in the airway: A case report.

A 75-year-old woman who had been taking methotrexate presented to our hospital for fever and dry cough. Chest computed tomography showed ground-glass opacity in the upper lobe of the right lung and foreign bodies in the lower lobe of the right bronchus. During bronchoscopy, foreign bodies were removed from the airway. We found increased levels of lymphocytes and a high CD4/CD8 ratio in the bronchoalveolar lavage fluid. Transbronchial lung biopsy revealed lymphocytic infiltration. Methotrexate was discontinued, and the imaging findings improved. Methotrexate-induced lung injury does occur unilaterally. Foreign bodies in the airway might also trigger unilateral methotrexate-induced lung injury.

Diagnosis of non-immediate hypersensitivity to amoxicillin in children by skin test and drug provocation tests: A retrospective case-series study.

BACKGROUND: Skin rash often occurs upon oral administration of amoxicillin in children, due to non-immediate hypersensitivity. However, information on delayed hypersensitivity to amoxicillin is scarce. Moreover, the appropriate diagnostic method and actual diagnostic rate of delayed hypersensitivity to amoxicillin among Japanese children are unclear. We conducted intradermal tests (IDTs) and drug provocation tests (DPTs) and retrospectively investigated the proportion of children with a definitive diagnosis of non-immediate hypersensitivity to amoxicillin. We then evaluated the characteristics of patients with a positive allergic workup. METHODS: We enrolled children referred for suspected findings of mild or moderate non-immediate hypersensitivity to amoxicillin between August 2018 and March 2020. If the IDT in the delayed phase was negative, DPT with amoxicillin (60-90 mg/kg/day) was performed for 7 days. Non-immediate hypersensitivity to amoxicillin was defined when IDT or DPT was positive. We evaluated the potential of the drug-induced lymphocyte stimulation test (DLST) to reveal hypersensitivity to amoxicillin. RESULTS: This study enrolled 27 children. Fourteen children (52%) had hypersensitivity to amoxicillin, of whom 12 had positive IDTs and two had positive DPTs. No differences in age, sex, history of allergic disease, days from oral use to symptom onset, type of rash at symptom onset, generalized rash, and DLST results were observed between the hypersensitivity and non-hypersensitivity groups. CONCLUSIONS: Examination should be performed for children with mild or moderate reactions because positive cases have no significant features and half of the suspected cases are negative.

A complicated case of Serratia marcescens catheter-related bloodstream infection misdiagnosed as hypersensitivity reactions to bicarbonate dialysate containing acetate.

Recurrent fever during/post-dialysis can occur due to infectious or non-infectious causes. We present the case of a 79-year-old patient who had persistent post-dialysis fever after long-term tunneled central venous catheterization with acetate-containing bicarbonate dialysate. Drug-induced lymphocyte stimulation test (DLST) was positive for acetate dialysate, and he was suspected of having acetate dialysate-induced hypersensitivity reaction. However, switching to acetate-free dialysate did not attenuate the fever. Since Serratia marcescens had been isolated twice from the blood, catheter-related bloodstream infection (CRBSI) was suspected. The culture of the catheter tip confirmed CRBSI caused by S. marcescens. Elevation of ß-d-glucan levels and appearance of pulmonary nodular shadow on chest computed tomography images indicated complicated fungal infections. Administration of antibiotics and antifungals led to resolution of the pulmonary nodular shadow with attenuation of fever and C-reactive protein levels. DLST for acetate dialysate was negative, and its reuse did not aggravate the symptoms; hence, the first result was considered false-positive. An indwelling catheter is a risk factor for S. marcescens-related CRBSI, which leads to post-dialysis fever. Hypersensitivity reactions to dialysates must be diagnosed considering the clinical course and DLST results.

Eosinophilic esophagitis induced by sublingual immunotherapy with cedar pollen: a case report.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease associated with eosinophilic infiltration of the esophageal mucosa mostly due to exposure to allergens. However, the causes and pathogenesis of EoE are not fully understood. We encountered a case of EoE that was triggered by sublingual immunotherapy (SLIT) for cedar pollen allergy. A 40-year-old man who was treated with Japanese cedar pollen tablet SLIT for cedar pollen allergy developed heartburn 3 weeks after the initiation of the treatment. He took vonoprazan for the heartburn, but the heartburn did not improve. Then, esophagogastroduodenoscopy was performed; it revealed longitudinal furrows and white spots on the esophageal mucosa, decreased vascular permeability, and erosions. Consequently, the patient was diagnosed with EoE. Heartburn and chest discomfort disappeared 1 week after the discontinuation of Japanese cedar pollen tablet SLIT, and the patient tested positive for drug allergy to Japanese cedar pollen tablet SLIT. In this study, we found that if heartburn persists during SLIT for cedar pollen allergy, and does not improve on administration of vonoprazan or proton pump inhibitors, EoE should be suspected. In addition, the occurrence of EoE due to drug allergy is indicated.